Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery
Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.846230/full |
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| author | Raquel E. Ajalik Raquel E. Ajalik Rahul G. Alenchery Rahul G. Alenchery John S. Cognetti Victor Z. Zhang Victor Z. Zhang James L. McGrath Benjamin L. Miller Benjamin L. Miller Hani A. Awad Hani A. Awad |
| author_facet | Raquel E. Ajalik Raquel E. Ajalik Rahul G. Alenchery Rahul G. Alenchery John S. Cognetti Victor Z. Zhang Victor Z. Zhang James L. McGrath Benjamin L. Miller Benjamin L. Miller Hani A. Awad Hani A. Awad |
| author_sort | Raquel E. Ajalik |
| collection | DOAJ |
| description | Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic. |
| first_indexed | 2024-12-22T06:26:38Z |
| format | Article |
| id | doaj.art-7d2bad37ea37494e8463c222c9b07b70 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-22T06:26:38Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-7d2bad37ea37494e8463c222c9b07b702022-12-21T18:35:50ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-03-011010.3389/fbioe.2022.846230846230Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic DiscoveryRaquel E. Ajalik0Raquel E. Ajalik1Rahul G. Alenchery2Rahul G. Alenchery3John S. Cognetti4Victor Z. Zhang5Victor Z. Zhang6James L. McGrath7Benjamin L. Miller8Benjamin L. Miller9Hani A. Awad10Hani A. Awad11Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesCenter for Musculoskeletal Research, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesCenter for Musculoskeletal Research, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesDepartment of Dermatology, University of Rochester, Rochester, NY, United StatesCenter for Musculoskeletal Research, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester, Rochester, NY, United StatesHuman Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic.https://www.frontiersin.org/articles/10.3389/fbioe.2022.846230/fullorgan-on-chiptissue-on-chipmicrophysiologic systemsmusculoskeletalmusclebone |
| spellingShingle | Raquel E. Ajalik Raquel E. Ajalik Rahul G. Alenchery Rahul G. Alenchery John S. Cognetti Victor Z. Zhang Victor Z. Zhang James L. McGrath Benjamin L. Miller Benjamin L. Miller Hani A. Awad Hani A. Awad Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery Frontiers in Bioengineering and Biotechnology organ-on-chip tissue-on-chip microphysiologic systems musculoskeletal muscle bone |
| title | Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery |
| title_full | Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery |
| title_fullStr | Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery |
| title_full_unstemmed | Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery |
| title_short | Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery |
| title_sort | human organ on a chip microphysiological systems to model musculoskeletal pathologies and accelerate therapeutic discovery |
| topic | organ-on-chip tissue-on-chip microphysiologic systems musculoskeletal muscle bone |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.846230/full |
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